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| ID | Type | Description | Link |
|---|---|---|---|
| U1111-1257-6851 | Registry Identifier | WHO |
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This is a Phase 1, multicenter, nonrandomized, open-label, parallel-group study in participants with mild or moderate hepatic impairment, and in participants with normal hepatic function.
Degrees of hepatic impairment will be determined during screening by the participant's score according to Pugh's Modification of Child's Classification of Severity of Liver Disease.
Participants will be enrolled in Groups 1 through 3 as follows:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ozanimod in subjects with mild hepatic impairment | Experimental | Participants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in subjects with mild hepatic impairment |
|
| Ozanimod in subjects with moderate hepatic impairment | Experimental | Participants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in subjects with moderate hepatic impairment |
|
| Ozanimod in healthy subjects | Experimental | Participants will receive ozanimod 0.23 mg once daily (QD) on Days 1 to 4, 0.46 mg QD on Days 5 to 7, and 0.92 mg QD on Day 8 in healthy subjects |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ozanimod | Drug | Ozanimod |
|
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics - AUClast on Day 8 (Ozanimod, CC112273 and CC1084037) | AUC from time zero to the last measured time point | Up to day 8 |
| Pharmacokinetics - AUC∞ on Day 8 (Ozanimod, CC112273 and CC1084037) | Area under the plasma concentration-time curve from time zero extrapolated to infinity | Up to day 8 |
| Pharmacokinetics - Cmax on Day 8 (Ozanimod, CC112273 and CC1084037) | Maximum observed plasma concentration | Up to day 8 |
| Pharmacokinetics - Cmin on Day 8 (Ozanimod, CC112273 and CC1084037) | Minimum observed plasma concentration | Up to day 8 |
| Pharmacokinetics - AUCtau on Day 8 (Ozanimod, CC112273 and CC1084037) | Area under the plasma concentration-time curve from time zero to dosing interval | Up to day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events (AEs) | An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a Participant during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the Participant's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE |
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Inclusion Criteria:
Acceptable methods of birth control in this study are the following:
All participants:
Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method are not acceptable methods of contraception.
Inclusion Criteria for Participants with Mild or Moderate Hepatic Impairment (Groups 1 and 2)
Each participant with mild or moderate hepatic impairment must satisfy the following criteria to be enrolled in the study:
Inclusion Criteria for Matched Normal Hepatic Function Participants (Group 3)
Each matched participant must satisfy the following criteria to be enrolled in the study:
Exclusion Criteria:
Exclusion Criteria for All Participants
The presence of any of the following will exclude a participant from enrollment:
Participant has any condition including the presence of laboratory abnormalities, which places the participant at unacceptable risk if he/she were to participate in the study.
Participant has any condition that confounds the ability to interpret data from the study.
Participant has a seated blood pressure outside 90 to 155 mmHg systolic or 50 to 95 mmHg diastolic at Screening or Day -1.
Participant has a seated pulse rate outside 55 to 90 beats per minute (bpm) at Screening or Day -1.
Participant has a positive serum test for human immunodeficiency virus (HIV) at Screening or Day -1.
Participant with any active infection including hepatitis.
Participant has a positive alcohol urine or breath test at Screening or Day -1.
Participant has received any investigational drug within 30 days or 5 times the elimination half-life (if known), whichever is longer, prior to the first dose of IP.
Participant has consumed pomelo-variety citrus fruits or juice (including pomelo, grapefruit, Seville oranges) within 7 days prior to the first dose of IP or herbal supplements including St. John's wort within 28 days prior to the first dose of IP.
Participant fails or is unwilling to abstain from strenuous physical activities for at least 24 hours prior to the first dose of IP.
Participant has poor peripheral venous access.
Participant has donated greater than 400 mL of blood within 60 days prior to Day 1.
Participant has history of hypersensitivity or allergic reaction to S1P receptor modulators.
Participant has used any of the following systemic medications:
Participant who in the last 6 months of signing the ICF experienced myocardial infarction, unstable angina, stroke, transient ischaemic attack, decompensated heart failure requiringmhospitalization or New York Heart Association (NYHA) Class III/IV heart failure.
Participant with history or presence of second-degree atrioventricular (AV) block Type II or third-degree AV block or sick sinus syndrome unless the patient has a functioning pacemaker.
Participant with history of cardiac arrest, cerebrovascular disease, uncontrolled hypertension, or severe untreated sleep apnoea, history of recurrent syncope or symptomatic bradycardia
Participant with pre-existing significant QT interval prolongation (QTc greater than 500 msec) or other risks for QT prolongation, and patients on medicinal products other than beta-blockers and calcium-channel blockers that may potentiate bradycardia.
Participant on class Ia (eg, quinidine, disopyramide) or class III (eg, amiodarone, sotalol) antiarrhythmic medicinal products, which have been associated with cases of torsades de pointes in patients with bradycardia have not been studied with ozanimod.
Exclusion Criteria for Participants with Hepatic Impairment (Groups 1 and 2)
The presence of any of the following will exclude a hepatically-impaired participant from enrollment:
Exclusion Criteria for Matched Normal Hepatic Function Participants (Group 3)
The presence of any of the following will exclude a matched normal hepatic function participant from enrollment:
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| Name | Affiliation | Role |
|---|---|---|
| Bristol-Myers Squibb | Bristol-Myers Squibb | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami Miller School of Medicine | Miami | Florida | 33136 | United States | ||
| Orlando Clinical Research Center OCRC |
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| Label | URL |
|---|---|
| BMS Clinical Trial Information | View source |
| BMS Clinical Trial Patient Recruiting | View source |
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|
| From the time the ICF is signed until 64 ± 3 days after the last dose of ozanimod treatment |
| Pharmacokinetics -Cmax on Days 1 and 5 (Ozanimod, CC112273 and CC1084037) | Maximum observed plasma concentration | Days 1 and 5 |
| Pharmacokinetics -Cmin on Days 1 and 5 (Ozanimod, CC112273 and CC1084037) | Minimum observed plasma concentration | Days 1, and 5 |
| Pharmacokinetics - AUCtau on Days 1 and 5 (Ozanimod, CC112273 and CC1084037) | Area under the plasma concentration-time curve from time zero to dosing interval | Days 1 and 5 |
| Pharmacokinetics - Tmax (Ozanimod, CC112273 and CC1084037) | Time to reach maximum observed plasma concentration | Days 1, 5, and 8 |
| Pharmacokinetics - AUClast (Ozanimod, CC112273 and CC1084037) | AUC from time zero to the last measured time point | From Day 8 till Day 72 |
| Pharmacokinetics - t1/2 (Ozanimod, CC112273 and CC1084037) | Terminal elimination half-life | From Day 8 till Day 72 |
| Pharmacokinetics - Vz/F (Ozanimod) | Apparent volume of distribution when dosed orally | From Day 8 till Day 72 |
| Pharmacokinetics - CL/F (Ozanimod) | Apparent total plasma clearance when dosed orally | From Day 8 till Day 72 |
| Pharmacokinetics - fu (Ozanimod, CC112273 and CC1084037) | Unbound fraction | Day 1 and Day 8 |
| Pharmacokinetics - Cmax,u (Ozanimod, CC112273 and CC1084037) | Maximum observed plasma concentration | Days 1, 5, and 8 |
| Pharmacokinetics - AUC∞,u (Ozanimod, CC112273 and CC1084037) | Unbound AUC∞ | From Day 8 till Day 72 |
| Pharmacokinetics - AUClast,u (Ozanimod, CC112273 and CC1084037) | Unbound AUClast | From Day 8 till Day 72 |
| Pharmacokinetics - AUCtau,u (Ozanimod, CC112273 and CC1084037) | Unbound AUCtau | Days 1, 5, and 8 |
| Pharmacokinetics - M/P AUCtau ratio (CC112273 and CC1084037) | Molecular weight corrected metabolite-to-parent AUC from time zero to dosing interval ratio | Days 1, 5, and 8 |
| Orlando |
| Florida |
| 32809 |
| United States |
| The Texas Liver Institute | San Antonio | Texas | 78215 | United States |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D008224 | Lymphoma, Follicular |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C000607776 | ozanimod |
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